Key result
Anthracycline administration in rats suppressed left ventricular ejection fraction by 10 to 40% compared to normal values in 71.7% of the 86 reviewed studies.
Why the study?
Preclinical animal models lack well-established objective criteria or reference values to uniformly characterize cardiotoxicity, which is not an endpoint in current general toxicology studies.
Systematic Review (n=86)
This review highlights the potential to establish objective echocardiographic criteria for anthracycline-induced cardiotoxicity in rat models for preclinical regulatory studies.
Reproducible LVEF suppression in rat anthracycline models supports preclinical research; clinical translation requires prospective human validation.
Anthracyclines are commonly used anticancer drugs with well‑known and extensively studied cardiotoxic effects in humans. In the clinical setting guidelines for assessing cardiotoxicity are well‑established with important therapeutic implications. Cardiotoxicity in terms of impairment of cardiac function is largely diagnosed by echocardiography and based on objective metrics of cardiac function. Until this day, cardiotoxicity is not an endpoint in the current general toxicology and safety pharmacology preclinical studies, although other classes of drugs apart from anthracyclines, along with everyday chemicals have been shown to manifest cardiotoxic properties. Also, in the relevant literature there are not well‑established objective criteria or reference values in order to uniformly characterize cardiotoxic adverse effects in animal models. This in depth review focuses on the evaluation of two important echocardiographic indices, namely ejection fraction and fractional shortening, in the literature concerning anthracycline administration to rats as the reference laboratory animal model. The analysis of the gathered data gives promising results and solid prospects for both, defining anthracycline cardiotoxicity objective values and delineating the guidelines for assessing cardiotoxicity as a separate hazard class in animal preclinical studies for regulatory purposes.
No takes yet. Share an insight, caveat, or question.
Georgiadis et al. (2020) conducted a systematic review in Anthracycline-induced cardiotoxicity (n=86). Anthracyclines vs. Normal baseline values was evaluated on Suppression of left ventricular ejection fraction (LVEF) and fractional shortening (LVFS). Anthracycline administration in rats suppressed left ventricular ejection fraction by 10 to 40% compared to normal values in 71.7% of the 86 reviewed studies.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: